Atlantic Health System

To report pregnancy outcome and neonatal immune parameters following early conception after maternal CD19 chimeric antigen receptor T-cell (CAR-T) therapy for refractory systemic lupus erythematosus (SLE). Maternal and neonatal CAR-T cells were assessed by transgene polymerase chain reaction (PCR) at delivery. CD19+ B-cell counts and immunoglobulin levels were measured in maternal and neonatal blood at birth. Infant health outcomes were assessed during the first year of life. Conception occurred approximately seven weeks after CD19 CAR-T infusion. CAR-T cells were not detected in maternal peripheral blood or cord blood at delivery. Neonatal CD19+ B-cell counts and IgG levels were within age-appropriate reference ranges and exceeded maternal values, which remained subnormal. During one year of follow-up, the infant experienced no recurrent or severe infections. This case represents the earliest reported pregnancy following CD19 CAR-T therapy for SLE and the first to include neonatal immune assessment at birth. No evidence of transplacental CAR-T transfer or clinically significant neonatal immunodeficiency was observed. Additional cases and long-term follow-up are required to guide reproductive counseling after CAR-T therapy.

<title>Abstract</title> Background Chest wall strapping (CWS) is a technique that restricts the chest wall to induce breathing at lower lung volumes. CWS increases lung elastic recoil and expiratory airflows. In computer tomography imaging studies CWS dilates small airways in healthy and COPD-subjects. Dynamic-dysanapsis describes the concept of airway dilation via interdependence of airways and lung parenchyma from CWS induced increase in lung elastance. The time course of CWS induced dynamic-dysnapsis is not defined. Volumetric capnography and plethysmography allow for repeated measurements of the lung structure function relationship. We hypothesized that CWS causes an increase in dead space of COPD-subjects via CWS induced increase in airway dimensions. Secondly, we hypothesized that CWS increases airway homogeneity and that these effects last for a period after removal of CWS. Methods After performing baseline measurements (ventilation parameters, plethysmography, and volumetric capnography) participants with COPD (n = 5) and healthy, sex-matched controls (n = 5) underwent CWS. Measurements were repeated every 15 minutes for one hour following CWS. After CWS-removal measurements were repeated every 15 minutes for an additional hour. We related anatomic dead space, alveolar dead space, V _D /V _T , and slope of the capnogram to lung volume and tracked their changes over time. Results Moving from unstrapped to the CWS and to post-CWS condition, we saw an overall increase in the anatomic dead space (a surrogate with the size of the airway tree) for both groups with CWS and post-CWS (p = 0.001). The capnographic slope is an indicator of airway uniformity. Post-CWS had a significant effect on both groups causing a decrease in the slope of the capnogram to lung volume ratio, showing a significant increase in airway homogeneity (p = 0.03). Conclusion CWS dilates airways quantified by the increase in dead space. The increase in airway homogeneity persists at least 45 minutes after strapping is removed. This indicates lasting benefits of CWS on airway function. The dilatation of airways and the improvement in airway homogeneity during and after CWS could facilitate enhanced delivery of inhaled therapies in COPD. CWS should be further investigated as a novel non-pharmacological treatment for COPD.

Abstract Background: Chest wall strapping (CWS) is a technique that restricts the chest wall to induce breathing at lower lung volumes. CWS increases lung elastic recoil and expiratory airflows. In computer tomography imaging studies CWS dilates small airways in healthy and COPD-subjects. Dynamic-dysanapsis describes the concept of airway dilation via interdependence of airways and lung parenchyma from CWS induced increase in lung elastance. The time course of CWS induced dynamic-dysnapsis is not defined. Volumetric capnography and plethysmography allow for repeated measurements of the lung structure function relationship. We hypothesized that CWS causes an increase in dead space of COPD-subjects via CWS induced increase in airway dimensions. Secondly, we hypothesized that CWS increases airway homogeneity and that these effects last for a period after removal of CWS. Methods: After performing baseline measurements (ventilation parameters, plethysmography, and volumetric capnography) participants with COPD (n=5) and healthy, sex-matched controls (n=5) underwent CWS. Measurements were repeated every 15 minutes for one hour following CWS. After CWS-removal measurements were repeated every 15 minutes for an additional hour. We related anatomic dead space, alveolar dead space, V D /V T , and slope of the capnogram to lung volume and tracked their changes over time. Results: Moving from unstrapped to the CWS and to post-CWS condition, we saw an overall increase in the anatomic dead space (a surrogate with the size of the airway tree) for both groups with CWS and post-CWS (p=0.001). The capnographic slope is an indicator of airway uniformity. Post-CWS had a significant effect on both groups causing a decrease in the slope of the capnogram to lung volume ratio, showing a significant increase in airway homogeneity (p=0.03). Conclusion: CWS dilates airways quantified by the increase in dead space. The increase in airway homogeneity persists at least 45 minutes after strapping is removed. This indicates lasting benefits of CWS on airway function. The dilatation of airways and the improvement in airway homogeneity during and after CWS could facilitate enhanced delivery of inhaled therapies in COPD. CWS should be further investigated as a novel non-pharmacological treatment for COPD.

The Evoque system is the first commercially available transcatheter tricuspid valve replacement (TTVR) system in the United States. However, challenging anatomy in real-world patients could preclude successful transfemoral Evoque TTVR. We aim to investigate the feasibility of the transjugular Evoque TTVR in anatomy unsuitable for a transfemoral approach. Eleven patients with challenging anatomy underwent transjugular Evoque TTVR at a high-volume center in the United States from February 2024 to January 2025, following an unsuccessful transfemoral attempt (n=9) or anatomic unsuitability (n=2). Procedural characteristics, intraprocedural success, periprocedural outcomes, echocardiographic findings, and 30-day clinical outcomes were assessed using the Tricuspid Valve Academic Research Consortium definitions. The procedural technique is provided in the accompanying supplement. Intraprocedural success was achieved in all 11 patients, with reasonable procedural time and no major procedural complications, except for 1 pacemaker implantation. At 30 days, the clinical success rate was 100%. Tricuspid regurgitation was reduced to none-to-trivial in 8 patients, mild in 2 patients, and moderate in 1 patient. There was no stroke, mortality, or rehospitalization. Nine out of 11 patients experienced an improvement in New York Heart Association functional class. In the largest single-center cohort of patients reported to date, transjugular Evoque TTVR demonstrated favorable intraprocedural, periprocedural, and short-term clinical outcomes, and was found to be a feasible alternative for patients with anatomy unsuitable for transfemoral Evoque TTVR.

Hearing has been identified as the largest modifiable mid-life risk factor for Alzheimer's Disease (AD), despite that its link to dementia remains unclear. Here we identify a biomarker of AD risk in an auditory neural signal using the non-invasive, rapidly acquired, and clinically translatable auditory brainstem response (ABR) in normal hearing knock-in rats (Swedish familial AD risk variant to Amyloid precursor protein, App S; male and female). While ABR morphology has been proposed as a biomarker for AD, we report a novel biomarker derived from multidimensional parametric feature extraction on the distribution statistics of repeated single traces of the ABR that increases its potential for clinical utility with sensitivity and specificity. We report accurate prediction of AD genetic risk in both young and aged animals: App S rats separate clearly from humanized controls in both sex- and age-dependent manners. Notably, auditory learning in young adulthood normalized the ABR signature in App S rats with maintained effects into older age, altogether supporting a central neural generator of auditory dysfunction related to AD risk. These preclinical findings show how ABRs could provide a very early biomarker for detection of AD risk and lay the groundwork to test the synergy of auditory and cognitive functions in human dementia.

BackgroundFemale patients with degenerative mitral regurgitation (DMR) can have worse mitral valve repair outcomes. We aim to study sex-specific differences in contemporary mitral transcatheter edge-to-edge repair (M-TEER).MethodsOne-year outcomes in prohibitive surgical risk patients with 3+/4+ DMR from the randomized CLASP IID trial were analyzed by sex.ResultsThe analysis population comprised 34.7% female patients (n = 102) and 65.3% male patients (n = 192). Female patients had significantly lower body mass index, fewer comorbidities, and smaller left ventricular indexed volumes and mitral valve area at baseline. At 1 year, there were no significant differences between female and male patients in survival (92.1% vs 90.9%, P = .754), freedom from heart failure hospitalization (91.7% vs 94.4%, P = .366), and freedom from major adverse events (86.0% vs 85.9%, P = .985), respectively. Both sexes achieved a significant reduction in mitral regurgitation from baseline at 1 year (P < .001), with comparable mitral regurgitation ≤1+ (75.6% vs 75.0%, P = 1.000). Baseline-adjusted changes in indexed left ventricular volumes (diastolic: –18.8 vs –15.7 mL, P = .087; systolic: –5.6 vs –5.0 mL, P = .645) and mitral gradients (+1.4 vs +1.1 mm Hg, P = .116) were similar, with no indication of stenosis. New York Heart Association class I/II was achieved in 86.4% of female patients vs 88.7% of male patients (P = .674), and the Kansas City Cardiomyopathy Questionnaire overall score increased by 14.1 vs 15.8 points (P = .502), respectively.ConclusionsIn the CLASP IID randomized trial, both sexes experienced high survival and freedom from major adverse events and heart failure hospitalization at 1 year post–M-TEER, with comparable improvements in echocardiographic, functional, and quality-of-life measures, despite differences in clinical presentation and the procedure. Results demonstrate that female patients achieve favorable safety and effectiveness outcomes, comparable to male patients, with contemporary M-TEER in DMR.